SAFETY/TOLERABILITY OF A ONE-TIME INFUSION OF LONVOGURAN ZICLUMERAN (LONVO-Z, NTLA-2002) FOR HEREDITARY ANGIOEDEMA

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Introduction Lonvoguran ziclumeran (lonvo-z, NTLA-2002) is an investigational, CRISPR-based, one-time infusion intended to treat hereditary angioedema (HAE). To date, lonvo-z has been well-tolerated and demonstrated clinical efficacy. We report updated safety/tolerability in patients receiving lonvo-z 50mg, focusing on adverse events reported within the first 24 hours after the start of infusion. Methods Twenty-one patients received one infusion of lonvo-z 50mg (initial lonvo-z 50mg, n=15; placebo-lonvo-z crossover, n=6) in the ongoing Phase 1/2 study (NCT05120830). Pretreatment (corticosteroids day before and day of infusion; H1/H2 blockers day of infusion) was administered. Results As of 12Feb25, treatment-emergent adverse events (TEAEs) occurred in 20/21 (95.2%) patients treated with lonvo-z 50mg; Day 1 TEAEs occurred in 13/20 (65%) patients. Infusion-related reactions (IRRs) occurred in 10/21 patients (47.6%), with rapid onset after infusion start (median [range] time to onset: 0.3 [0-8.2] hours). IRR symptoms occurring in >1 patient: headache (n=3), nausea (n=2), and fever (n=2). Symptom duration varied (median [range]: 8.4 hours [12 min to 21.3 days]). All IRRs resolved; in 8/10 patients, symptoms resolved in <24 hours; 2 patients had IRR symptoms lasting >24 hours (headache, 22 days; increased thirst, 7 days). Four patients received treatment for IRRs: dexamethasone (n=3), acetaminophen (n=2), and ibuprofen (n=2). Two patients required infusion rate change/interruption; none discontinued the infusion. Conclusion A one-time infusion of lonvo-z 50mg was well-tolerated, resulting in high rates of attack-free and LTP-free status in patients. Most IRRs occurred shortly after infusion and resolved same day. All patients received the full dose of lonvo-z.

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